Data from ferret experiments supports the recommendation of a 10-day quarantine when ferrets bite people or other animals. There are no similar studies in species other than dogs, cats, and ferrets and it is not appropriate to use quarantine to rule-out the risk of rabies transmission to humans or other animals in other small mammals.

Introduction

Rabies is an acute, disseminated encephalomyelitis of mammals caused by a virus of the family Rhabodiviridae. Transmission generally occurs through a bite from an infected animal. The bite wound allows introduction of the virus, which is shed in the saliva. Following the bite, local replication of the virus occurs in myocytes with eventual penetration of the virus into the peripheral nerves. Spread to the central nervous system (CNS) occurs through afferent neurons. During this process, the animal is asymptomatic and incapable of transmitting the virus. Symptoms consistent with damage to the CNS begin shortly after the virus enters the brain. The virus continues to travel back out of the CNS through efferent neurons and quickly enters the salivary glands. It is at this point that the animal becomes capable of transmitting the infection and there may be a short period of time (usually considered to be a few days) during which the animal is infectious but not yet showing signs of disease. Although rabies is almost uniformly fatal once symptoms develop, not all animals exposed to the virus will develop disease. Careful review of the literature reveals scattered reports of apparent symptomatic rabies with eventual recovery. Survival following symptomatic disease remains an extremely rare event.

Epidemiology

There are multiple variants of the virus, which can be differentiated genetically. Each variant is adapted to a specific reservoir species and it is that species which maintains the virus in the environment. Spillover from the reservoir host to other species occurs with all virus variants. However, the extent to which spillover occurs is somewhat dependent upon both the virus variant and the natural history of the reservoir host.

Canine rabies, or rabies caused by the canine adapted variant of this virus, remains the most common type of rabies in most of the developing world. In North America and much of Europe, mandatory dog vaccination and stray animal control campaigns have eliminated endemic transmission of this rabies variant. Reintroduction of the virus through animal importation remains a constant risk. In places where canine rabies has been controlled, different variants of the virus exist in various wildlife reservoir species. In the United States (US), for example, seven separate terrestrial rabies variants (raccoon, north central skunk, south central skunk, California skunk, arctic fox, Arizona grey fox, Texas grey fox) exist in different reservoir species and an eighth variant, mongoose, exists in Puerto Rico.

It is noteworthy that spillover of rabies virus to other species in the US is significantly more common with the raccoon variant of the virus than with any other variety (Figure 2). This is likely due to a combination of viral variant characteristics, the successful adaptation of raccoons to human urban and suburban habitats, the overlap of high human population densities with high raccoon population densities and the generally social behavior of the raccoon species.

Figure 2. Comparison of distribution of rabid raccoons, skunks, foxes, and dogs and cats in the United States and Puerto Rico. Note the concentration of cases along the East Coast occurring as a result of the raccoon variant of the virus. Photo credit: Blanton 2012. Publicly available at http://www.cdc.gov/rabies/pdf/2011-us-surveillance.pdf. Click image to enlarge.

Rabies in small wildlife species

All mammals are considered to be susceptible to rabies although susceptibility appears to vary by species and viral variant. There are two general clinical forms of the disease, excitatory or “furious” rabies, and paralytic or “dumb” rabies (Lackay 2008). Animals may display one or both of those forms as the disease progresses. Although specific species may have a tendency to one form or the other, there is not enough consistency for this to be used as diagnostic criteria. Nor is there any sign pathognomonic for rabies; therefore, rabies should be included in the differential diagnosis during the evaluation of any neurologic mammal, especially following an appropriate exposure to a suspect or confirmed rabid animal.

Rodents and lagomorphs are rarely reported as rabid, with a few exceptions (Table 1). It is thought that most small mammals exposed to a rabid raccoon or skunk, will not survive the encounter long enough to go on to develop rabies. Spillover of bat strains of the rabies virus into small mammals has also been reported (Webster 1988). In theory, these encounters would not immediately lead to the death of the animal suggesting a greater likelihood of survival sufficient to allow development of disease. It has been proposed that wild small mammal species that utilize attics of dwellings might pose a greater risk for rabies since this living space may put them in direct proximity to colonial bat species that also prefer attics as roosting spots. In practice however, isolation of a bat strain of rabies virus from small mammals remains an extremely rare event.

Groundhogs (Marmota monax), also known as woodchucks, are the most commonly reported rabid rodent species in the US. (Blanton 2012, Childs 1997, Fishbein 1986) Given an average weight of around 10 pounds (4.5 kg), it is theorized that they are more likely to survive an encounter with a rabid animal thereby explaining the relative frequency with which they are found to be rabid. Beavers (Castor canadensis) are also increasingly found to be rabid in the US. Rabies in both species has resulted from spillover of the raccoon strain of the virus.

Rabies in pet exotics

Due to the increase in the popularity of ferrets (Mustela putorius furo) as pets in the 1990s, more research involving experimental infection and viral shedding periods has been conducted in this species than in most other small exotic pets (Niezgoda 1997, Niezgoda 1998). This research, conducted using two separate virus variants, showed that ferrets exposed to rabies virus had mean incubation periods of 28-33 days and a mean symptomatic period of 4-5 days. Common clinical signs included ascending paralysis, anorexia, cachexia, bladder atony, tremors, and paresis. Symptoms that varied somewhat by virus strain included pyrexia versus hypothermia, and lethargy versus hyperactivity. Cases of naturally occurring rabies in pet ferrets are rare (Table 1), probably due to a combination of lack of opportunities for exposure and the availability of an effective vaccine.

Natural infection of pet rabbits (Oryctolagus cuniculus) and a guinea pig (Cavia porcellus) has also been documented (Table 1). Of the 13 rabbits and one guinea pig detailed in the literature (Eidson 2005, Karp 1999), incubation periods ranged from 21-46 days for those with known exposures. Seven of 13 rabbits reportedly showed limb paresis or paralysis as one sign and five of the remaining six are described only as having neurologic signs. The guinea pig and one rabbit were not described as having neurologic disease although in both cases a bite to the owner could be considered to represent a neurologic manifestation of the disease. All of these cases were in animals housed outdoors where the animal could be partially accessed by wild animals. All but two of these cases occurred in areas where raccoon rabies is the circulating terrestrial strain. No licensed vaccine exists for use in these species. Prevention relies upon decreasing opportunities for exposure. If housed outdoors, animals should be kept in double-walled enclosures without exposed wire mesh floors and not allowed to roam freely unsupervised (Lackay 2008).

Other species kept as exotic pets for which at least one individual has been found to be rabid in the US are the chinchilla (Chinchilla lanigera) and the Norway rat (Rattus norvegicus).

Diagnosis

There are no pathognomonic signs for diagnosing rabies in the living animal. The gold standard of rabies diagnosis continues to be the direct fluorescent antibody test on brain tissue. This test is rapid, inexpensive and both highly sensitive and highly specific. Because virus distribution within the brain tissue can vary some, diagnosis requires a full cross-section sample of brainstem (Centers for Disease Control) and many diagnostic laboratories require samples from both lobes of the cerebellum as well. No single reliable antemortem test for rabies exists. Antemortem diagnosis in humans requires submission of serum, cerebral spinal fluid, saliva and a nuchal biopsy and variability in patterns of positivity within these four samples between patients has been observed. The realities of intermittent viral shedding in saliva and limits in the technology’s ability to detect small amounts of viral RNA present in small amounts of saliva means that no reliable antemortem test in animals is foreseeable in the near future.

Zoonotic concerns

Rabies is a rare cause of human morbidity and mortality in the developed world. In parts of the world where canine rabies remains endemic, it is estimated to cause at least 50,000 human deaths annually. Exposure to the virus generally occurs via a bite from an infected animal. Introduction of infective material (saliva or central nervous system tissue) into a scratch or mucous membrane also represents an exposure. Contact between infective material and intact skin does not constitute an exposure. Blood, urine, fecal material and skunk spray are not infectious and should not be treated as such. Rarely, transmission has also occurred through corneal and solid organ transplantation. In very isolated, specific circumstances, aerosol transmission of the virus has also occurred in a heavily bat-infested cave and a rabies vaccine laboratory.

No human cases of rabies transmitted by rodents or lagomorphs have been documented in the US or Europe and rabies in small wild mammals and exotic pets is exceedingly rare. Despite this, the almost uniformly fatal nature of the disease leaves little room for error when assessing the possibility of human exposure. The early experimental work with rabies virus in wild rodents demonstrates that they are capable of shedding the virus in their saliva following disease development (Winkler 1972). The experimental work with ferrets shows that virus was present in the saliva of 47% of infected ferrets and was found between 2 days prior to symptom onset and 6 days after (Niezgoda 1998).

Evaluating the risk of rabies transmission from a small wild mammal or exotic pet should always be done in conjunction with local public health authorities. Information about how long an exotic pet has been owned, where it was obtained, how it is housed and whether or not it is allowed any unsupervised outdoor activity is all critical to accurately assessing risk. Circumstances involving neurologic animals caged outdoors in such a way that a raccoon or skunk could gain sufficient access to expose the animal, should carry a higher index of suspicion for rabies than those housed completely strictly indoors.

Although local statutes and regulations regarding rabies control vary, the data from the ferret experiments are generally used to support the recommendation of a 10 day quarantine for ferrets that bite people or other animals. Ten-day quarantine presumes that a bite could represent the first sign of rabies onset; if the animal survives for 10 days following the incident, these data suggest that rabies virus was not present in saliva at the time of the bite and therefore transmission of the virus did not occur. Ten-day quarantine is applied regardless of the vaccination status of the animal. Since no similar studies have been done with other small mammal species, quarantine is not considered to be appropriate to rule-out the risk of rabies transmission to humans or other animals in any species other than dogs, cats and ferrets.

Table 1. Rabid non-reservoir wildlife species and exotic pets in the US, 1990-1999

Table 1. Rabid non-reservoir wildlife species and exotic pets in the United States, 1990-1999.

Species

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

Total

Beaver

3

1

3

2

2

5

3

3

22

Chinchilla

Chipmunk

1

1

2

Coati

Ferret

2

1

1

2

3

1

1

11

Fisher

2

2

2

6

Ground Squirrel

Groundhog

25

55

52

59

54

50

43

55

63

40

496

Guinea Pig

Mink

1

1

Mongoose

33

54

51

34

56

23

36

53

35

59

434

Muskrat

1

1

1

3

Nutria

1

1

Opossum

2

6

4

2

2

3

2

3

3

2

29

Rabbit

1

2

3

1

4

1

2

3

2

1

20

Rat

Ringtail

2

2

3

1

8

Shrew

1

1

2

Squirrel

1

1

1

1

2

1

7

Weasel

1

1

Species

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

Total

Table 2. Rabid non-reservoir wildlife species and exotic pets in the US, 2000-2012

Table 2. Rabid non-reservoir wildlife species and exotic pets in the United States, 2000-2012.